Multicomponent reactions – those where three or more substrates combine into a product – have been highly useful in rapidly building chemical building blocks of increased complexity4, but achieving this enzymatically has remained rare.5 This limitation primarily arises because an enzyme’s active site is not typically set up to address multiple substrates, especially in cases involving multiple radical intermediates6. Recently, chemical catalytic radical sorting has emerged as an enabling strategy for a variety of useful reactions7,8. However, making such processes enantioselective is highly challenging due to the inherent difficulty in the stereochemical control of radicals9. Here, we repurpose a thiamine-dependent enzyme10,11 through directed evolution, combine it with photoredox catalysis, to achieve a photobiocatalytic enantioselective three-component radical cross-coupling. This approach combines three readily available starting materials — aldehydes, α-bromo-carbonyls and alkenes — to give access to enantioenriched ketone products. Mechanistic investigations provide insights into how this dual photo-/enzyme system precisely directs the three distinct radicals involved in the transformation, unlocking new enzyme reactivity. Our approach has achieved exceptional stereoselectivity, with 25 out of 33 examples achieving ≥97% enantiomeric excess.